Affected mutation carriers with CTLA-4 insufficiency can present in any medical specialty. Family members should be counseled because disease manifestation can occur as late as 50 years of age. EBV- and cytomegalovirus-associated complications must be closely monitored. Treatment interventions should be coordinated in clinical trials.

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Regulatory T cells (T ) control immune responses by suppressing various inflammatory cells. T in newborn babies may play an important role in preventing excessive immune responses during their environmental change. We examined the number and phenotype of T during the neonatal period in 49 newborn babies. T were characterized by flow cytometry using cord blood (CB) and peripheral blood (PB) from the early (7-8 days after birth) and late (2-4 weeks after birth) neonatal periods. CD4 forkhead box protein 3 (FoxP3 ) T cells were classified into resting T (CD45RA FoxP3 ), activated T (CD45RA FoxP3 ) and newly activated T cells (CD45RA FoxP3 ). Compared with CB and PB during the late neonatal period, the percentage of T and all T subpopulations in the CD4 lymphocyte population were increased significantly during the early neonatal period. Furthermore, the proportion and absolute number of activated T were increased markedly compared with other T subpopulations, such as resting T and newly activated T cells (non-T ), in the early neonatal period. Increased T concomitantly expressed the suppressive molecule cytotoxic T lymphocyte antigen-4 (CTLA-4). The up-regulated expression of chemokine receptor 4 (CCR4) and down-regulated expression of CCR7 were also observed in expanded T . When cord blood cells were cultured in vitro with CD3 monoclonal antibodies (mAb) for 5 days, CD4 CD45RA FoxP3 cells were increased significantly during the culture. Thus, the presence of increased activated T in early neonates may play an important role in immunological regulation by suppressing excessive T cell activation caused by the immediate exposure to ubiquitous antigens after birth.

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Our findings suggest a shift of Th1-dominant to Th2-dominant status by vaccination might play important roles in maintaining successful pregnancies. Induction of some T cells that utilize different TCR repertoires possibly suppresses maternal rejection reactions.